Genomic vs nongenomic actions of thyroid hormones: changes of paradigms, physiological implications and therapeutical perspectives

• Grant number: 13/05629-4
• Support Opportunities: Research Projects - Thematic Grants
• Duration: May 01, 2014 - April 30, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Tereza Nunes
• Grantee: Maria Tereza Nunes
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais: Celia Regina Nogueira
• Associated researchers: Andréa da Silva Torrão ; Angelo Rafael Carpinelli ; Claudimara Ferini Pacicco Lotfi ; Francemilson Goulart da Silva ; Martin Elliot Young ; Paul Webb ; Pedro Alexandre Favoretto Galante ; Roberto Barbosa Bazotte ; STANKO S. STOJILKOVIC
• Associated scholarship(s): 17/10059-3 - Determination of er± and ER² receptor participation in the action of triiodotironine (T3) in modulation of PR gene expression in MCF-7 breast adenocarcinoma cells, BP.IC; 17/21875-6 - Triiodothyronine (T3) treatment effects on miRNA expression profile in type 1 diabetes mellitus and obesity: importance and therapeutic implications, BP.PD; 16/05393-9 - Evaluation of the proinflammatory and antinflammatory cytokines and TSH receptor expression in subcutaneous and periepididymal adipose tissue of Wistar rats subjected to cafeteria diet: effect of thyroid hormone, BP.IC; + associated scholarships 14/25888-7 - Characterization of the molecular basis involved on the expression of circadian clock genes in the pituitary at different thyroid states and the consequences for the synthesis/secretion of anterior pituitary hormones, BP.PD; 15/09686-8 - Mechanism of action of triiodothyronine hornone (T3) in the TGFa gene expression in breast adenocarcinoma cell lines, BP.IC; 14/15209-5 - PARTICIPATION OF T3 IN POST-TRANSCRIPTIONAL CONTROL OF HIF-1± AND TGF± EXPRESSION IN CELL LINES OF BREAST CANCER AND EVALUATION OF THE INVOLVEMENT OF POTENTIAL miRNAS, BP.DR; 14/15966-0 - The role of BDNF in the central nervous system associated with hyperthyroidism and diabetes mellitus, BP.MS - associated scholarships

Abstract

Thyroid hormones (TH) play essential roles in complex biological processes by regulating the expression of genes/proteins involved in metabolism, growth and development; these actions are known as genomic. However, some TH actions, known as nongenomic, occur in the presence of inhibitors of gene transcription, are rapidly triggered, and are elicited by T2 and rT3, classically considered as inactive metabolites of TH. Many TH genomic actions are well recognized, but some of them have been poorly explored, as those related with cognitive processes, heart metabolism, stress and energetic homeostasis. Even less is known about the nongenomic actions of TH, their targets, binding sites and signaling pathways and, the comprehension of the mechanisms involved in these actions could have a great potential of use in situations in which the chronic use of TH, although desirable, could be deleterious. This question becomes extremely relevant considering that thyroid dysfunction is the second more prevalent endocrine disease in the world. Moreover, the occurrence of thyroid dysfunction increases with aging, when the association with cognitive, cardiovascular and energetic homeostasis impairment increases, and that the association between thyroid diseases and diabetes is high. Therefore, this study aims to explore the genomic actions of TH, metabolites and agonists in the processes indicated above and their molecular basis, as well as to identify new targets, mechanisms and potentialities of the nongenomic actions of TH. We consider that the development of this study will enlarge the knowledge on this issue and point to interesting therapeutic perspectives, thus enabling the implementation of intervention strategies. (AU)

Scientific publications

(18)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TABATA M. SILVA; FERNANDA C. F. MORETTO; MARIA T. DE SIBIO; BIANCA M. GONÇALVES; MIRIANE OLIVEIRA; REGIANE M. C. OLIMPIO; DIEGO A. M. OLIVEIRA; SARAH M. B. COSTA; IGOR C. DEPRÁ; VICKELINE NAMBA; et al. Triiodothyronine (T3) upregulates the expression of proto-oncogene TGFA independent of MAPK/ERK pathway activation in the human breast adenocarcinoma cell line, MCF7. ARCHIVES OF ENDOCRINOLOGY METABOLISM, v. 63, n. 2, p. 142-147, 2019-03-21. (13/05629-4, 15/09686-8, 14/15209-5)

DA SILVA TEIXEIRA, S.; FILGUEIRA, C.; SIEGLAFF, D. H.; BENOD, C.; VILLAGOMEZ, R.; MINZE, L. J.; ZHANG, A.; WEBB, P.; NUNES, M. T.. 3,5-diiodothyronine (3,5-T2) reduces blood glucose independently of insulin sensitization in obese mice. ACTA PHYSIOLOGICA, v. 220, n. 2, p. 238-250, JUN 2017. (10/18151-7, 12/17430-5, 13/05629-4)

PANVELOSKI-COSTA, ANA CAROLINA; TATAGIBA KUWABARA, WILSON MITSUO; MUNHOZ, ANA CLAUDIA; LUCENA, CAMILA FERRAZ; CURI, RUI; CARPINELLI, ANGELO RAFAEL; NUNES, MARIA TEREZA. The insulin resistance is reversed by exogenous 3,5,3 ` triiodothyronine in type 2 diabetic Goto-Kakizaki rats by an inflammatory-independent pathway. ENDOCRINE, v. 68, n. 2, SI, JAN 2020. (17/21875-6, 13/05629-4)

SERRANO-NASCIMENTO, CAROLINE; MORILLO-BERNAL, JESUS; ROSA-RIBEIRO, RAFAELA; NUNES, MARIA TEREZA; SANTISTEBAN, PILAR. Impaired Gene Expression Due to Iodine Excess in the Development and Differentiation of Endoderm and Thyroid Is Associated with Epigenetic Changes. THYROID, v. 30, n. 4, JAN 2020. (13/05629-4, 12/24391-6, 16/18517-8, 15/16695-3)

PANVELOSKI-COSTA, ANA C.; SERRANO-NASCIMENTO, CAROLINE; BARGI-SOUZA, PAULA; POYARES, LEONICE L.; VIANA, GABRIELA DE S.; NUNES, MARIA T.. Beneficial effects of thyroid hormone on adipose inflammation and insulin sensitivity of obese Wistar rats. PHYSIOLOGICAL REPORTS, v. 6, n. 3, FEB 2018. (13/05629-4, 11/09014-9)

PELICIARI-GARCIA, RODRIGO A.; BARGI-SOUZA, PAULA; YOUNG, MARTIN E.; NUNES, MARIA TEREZA. Repercussions of hypo and hyperthyroidism on the heart circadian clock. CHRONOBIOLOGY INTERNATIONAL, v. 35, n. 2, p. 147-159, 2018. (13/05629-4, 14/25888-7)

ROMANO, RENATA MARINO; BARGI-SOUZA, PAULA; BRUNETTO, ERIKA LIA; GOULART-SILVA, FRANCEMILSON; SALGADO, RENATO M.; TENORIO ZORN, TELMA MARIA; NUNES, MARIA TEREZA. Triiodothyronine differentially modulates the LH and FSH synthesis and secretion in male rats. ENDOCRINE, v. 59, n. 1, p. 191-202, JAN 2018. (09/17822-8, 13/05629-4)

PRIETO-ALMEIDA, FERNANDA; PANVELOSKI-COSTA, ANA CAROLINA; CRUNFLI, FERNANDA; TEIXEIRA, SILVANIA DA SILVA; NUNES, MARIA TEREZA; TORRAO, ANDREA DA SILVA. Thyroid hormone improves insulin signaling and reduces the activation of neurodegenerative pathway in the hippocampus of diabetic adult male rats. Life Sciences, v. 192, p. 253-258, JAN 1 2018. (14/06372-0, 14/15966-0, 13/05629-4, 10/18151-7, 11/09014-9)

PELICIARI-GARCIA, RODRIGO ANTONIO; PREVIDE, RAFAEL MASO; NUNES, MARIA TEREZA; YOUNG, MARTIN ELLIOT. Interrelationship between 3,5,3 `-triiodothyronine and the circadian clock in the rodent heart. CHRONOBIOLOGY INTERNATIONAL, v. 33, n. 10, p. 1444-1454, 2016. (13/05629-4)

TOMIC, MELANIJA; BARGI-SOUZA, PAULA; LEIVA-SALCEDO, ELIAS; NUNES, MARIA TEREZA; STOJILKOVIC, STANKO S.. Calcium signaling properties of a thyrotroph cell line, mouse T alpha T1 cells. Cell Calcium, v. 58, n. 6, p. 598-605, DEC 2015. (13/05629-4, 12/06643-8)

SILVA, TABATA M.; MORETTO, FERNANDA C. F.; DE SIBIO, MARIA T.; GONCALVES, BIANCA M.; OLIVEIRA, MIRIANE; OLIMPIO, REGIANE M. C.; OLIVEIRA, DIEGO A. M.; COSTA, SARAH M. B.; DEPRA, IGOR C.; NAMBA, VICKELINE; et al. Triiodothyronine (T-3) upregulates the expression of proto-oncogene TGFA independent of MAPK/ERK pathway activation in the human breast adenocarcinoma cell line, MCF7. ARCHIVES OF ENDOCRINOLOGY METABOLISM, v. 63, n. 2, p. 142-147, MAR-APR 2019. (15/09686-8, 14/15209-5, 13/05629-4)

BARGI-SOUZA, P.; GOULART-SILVA, F.; NUNES, M. T.. Novel aspects of T-3 actions on GH and TSH synthesis and secretion: physiological implications. JOURNAL OF MOLECULAR ENDOCRINOLOGY, v. 59, n. 4, p. R166-R177, NOV 2017. (14/25888-7, 12/06643-8, 09/17813-9, 13/05629-4)

PREVIDE, RAFAEL MASO; WANG, KAI; SMILJANIC, KOSARA; JANJIC, MARIJA M.; NUNES, MARIA TEREZA; STOJILKOVIC, STANKO S.. Expression and Role of Thyrotropin Receptors in Proopiomelanocortin-Producing Pituitary Cells. THYROID, JAN 2021. (13/05629-4)

SERRANO-NASCIMENTO, CAROLINE; SALGUEIRO, RAFAEL BARRERA; PANTALEAO, THIAGO; CORREA DA COSTA, VANIA MARIA; NUNES, MARIA TEREZA. Maternal Exposure to Iodine Excess Throughout Pregnancy and Lactation Induces Hypothyroidism in Adult Male Rat Offspring. SCIENTIFIC REPORTS, v. 7, NOV 15 2017. (12/24391-6, 13/05629-4)

PANVELOSKI-COSTA, A. C.; TEIXEIRA, S. SILVA; RIBEIRO, I. M. R.; SERRANO-NASCIMENTO, C.; DAS NEVES, R. X.; FAVARO, R. R.; SEELAENDER, M.; ANTUNES, V. R.; NUNES, M. T.. Thyroid hormone reduces inflammatory cytokines improving glycaemia control in alloxan-induced diabetic wistar rats. ACTA PHYSIOLOGICA, v. 217, n. 2, p. 130-140, JUN 2016. (10/18151-7, 11/09014-9, 13/05629-4)

SERRANO-NASCIMENTO, CAROLINE; SALGUEIRO, RAFAEL BARRERA; VITZEL, KAIO FERNANDO; PANTALEAO, THIAGO; CORREA DA COSTA, VANIA MARIA; NUNES, MARIA TEREZA. Iodine excess exposure during pregnancy and lactation impairs maternal thyroid function in rats. ENDOCRINE CONNECTIONS, v. 6, n. 7, p. 510-521, OCT 1 2017. (12/24391-6, 13/05629-4)

TEIXEIRA, SILVANIA DA SILVA; PANVELOSKI-COSTA, ANA C.; CARVALHO, ALINE; MONTEIRO SCHIAVON, FABIANA P.; RUIZ MARQUE, ANY DE CASTRO; CAMPELLO, RAQUEL S.; BAZOTTE, ROBERTO B.; NUNES, MARIA T.. Thyroid hormone treatment decreases hepatic glucose production and renal reabsorption of glucose in alloxan-induced diabetic Wistar rats. PHYSIOLOGICAL REPORTS, v. 4, n. 18, SEP 2016. (10/18151-7, 11/09014-9, 13/05629-4)

BARGI-SOUZA, PAULA; GOULART-SILVA, FRANCEMILSON; NUNES, MARIA TEREZA. Posttranscriptional actions of triiodothyronine on Tshb expression in T alpha T1 cells: New insights into molecular mechanisms of negative feedback. Molecular and Cellular Endocrinology, v. 478, p. 45-52, DEC 15 2018. (13/05629-4, 09/17813-9, 14/25888-7)